The objectives of this research are to explore the pharmacology and toxicology of potential vasodilator drugs modeled after nitroprusside. Our previous discovery that nitroprusside can penetrate the intact human red cell and react with hemoglobin to generate methemoglobin and cyanmethemoglobin and to liberate free cyanide defined one toxic or even lethal effect of acute overdosage of nitroprusside. Since cyanide is metabolized in vivo to thiocyanate this discovery also defined the potential for chronic toxicity with nitroprusside administration over prolonged periods. Thiocyanate accumulation can lead to goiter or to central nervous system derangements. We are synthesizing a series of nitroso coordination complexes of ruthenium and testing them for their effects on blood pressure in comparison with nitroprusside and with nitrite. We are also attempting to define the fundamental toxic effects of ruthenium salts and complexes. some of these complexes will also be screened to see if they have antitumor activity which is of interest for further study. We are also exploring the pathophysiologic basis for high altitude hemoglobinemia and rational methods for treating acute hydrogen sulfide poisoning.